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Chris Masterjohn on Cholesterol & Heart Disease (Part 2)


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This week we’re glad to welcome Chris Masterjohn back to the show. Chris joined us on Episode 11 to discuss the role of cholesterol in heart disease, and to dispel the many myths associated with those subjects. There was so much to cover, we had to have Chris back for part 2 (and in fact, we still didn’t cover all of the material so he’s going to come back for part 3 in the future!)

In this episode, we discuss (among other things):

  • what is a “normal” cholesterol? what can anthropological studies tell us about this?
  • are lipoprotein particle size tests accurate? what’s the best way of determining particle size?
  • why do some people have high cholesterol (TC & LDL) after adopting a Paleo/WAPF diet? is this something to be concerned about?

Enjoy the show!

Full Text Transcript

Danny: Hello everyone and welcome to the Healthy Skeptic podcast. My name is Danny Roddy of DannyRoddy.com and with me is Chris Kresser, health detective and owner of ChrisKresser.com, a blog challenging mainstream myths about nutrition and health. Chris, how are you doin’ buddy?

Chris Kresser: I’m great Danny, how about you, how’s Hawaii?

Danny: It’s amazing I can’t ask to spend any more time sitting in the sand looking at the water, it’s amazing.

Chris Kresser: Yeah I admit to some mild jealousy at the moment. I feel like I’ve been a hermit for the past 6 weeks, it’s been amazing spending that time with my daughter but my typical routine at this time of the year is to be out in the sun a lot and surfing and things like that. It’s been more along the changing diapers line lately.

Danny: To be honest I’ve been looking forward the whole trip to interviewing our special guest.

Chris Kresser: We’ve got Chris Masterjohn here back for part 2 of the cholesterol special we’re really happy to have him back. The first show that we did with him was one of our most popular shows ever, and people have been really excited to hear the second part. So Chris, why don’t we do like a 2 minute synopsis of the last show, just for people who might have missed it so they’re not completely lost, and then we’re gonna talk a little bit about some more basics about cholesterol that we didn’t get to during the last show, and then we’re gonna answer a few questions. So why don’t you take it from here Chris.

Chris Masterjohn: Alright, sounds great. Thank you so much it’s great to be here again Chris and Danny, thanks for having me on a second time. So last time we talked about whether cholesterol plays any role in heart disease and of course the roles of cholesterol in the body. Cholesterol does a lot of important things it’s the precursor to sex hormones, highly related molecules the precursor to vitamin D, it’s the precursor to bile acids which help our digestion and so on. But our big concern is does cholesterol cause heart disease and when we go to the doctor and get our blood lipids measured does that have any significance for us. There seemed to be two different camps, where we have the mainstream that says cholesterol is one of the most important causes of heart disease, when its level in the blood rises that cholesterol just kind of bursts into the arterial wall and causes an atherosclerotic plaque. Some of these people, even the nobel prize winning scientists like Michael Brown and Joseph Goldstein call themselves cholesterol warriors cause they’re making a war on cholesterol. Then we have the opposite side of spectrum which are the cholesterol skeptics and they say no, these blood lipids don’t really have anything to do with heart disease. And so they say this idea that they do, the lipid hypothesis, is just totally false. And so what I presented in the last show was basically an attempt to reconcile the evidence that’s used on both sides of this argument. And what I like to say is that the infiltrative lipid hypothesis is false, but the degenerative lipid hypothesis would be a good term for what the science is leading us towards. The reason I use those is words is because when the role of blood lipids in heart disease was first discovered in the cholesterol-fed rabbit model, Nicolai Anitschkov who basically brought that model to the fore said it’s not about degeneration of the arterial wall, it’s about this high concentration of lipids in the blood that’s infiltrating the blood vessel wall. And last time we talked about all the evidence that suggests that it is lipid related so we should have some type of lipid hypothesis, but it’s not about the high concentration, it’s not about the high amount. It’s about the degeneration of those lipoproteins in the blood that are carrying those lipids. So what we wanna do is not seek how to lower the concentration of lipids necessarily but we wanna seek how to prevent the degeneration of those lipids, and we briefly talked about the need to maintain robust thyroid hormone status and good metabolism. The need to get sufficient nutrients to minimize the degeneration of these lipids, and the need to minimize inflammation, infection, and other toxic factors that contribute to their degeneration. So that’s the basic rundown of the last show.

Chris Kresser: Right, he got a lot of things right but he got that one key point wrong. And that seems to have set us on a path that has really distorted what we know now to be true.

Chris Masterjohn: Absolutely, because of the simple reason that there are some things that relative to other things might raise the concentration of cholesterol in the blood, but those things are sometimes things that are actually really good for us when we look at the bottom line.

Chris Kresser: Yeah, and I think that’s what’s been confusing about this for some people is that neither of the extremes are right there’s a little bit of truth on both sides and so it’s been really difficult to tease out exactly what we can determine from the scientific literature, at least the current scientific literature. So let’s talk a little bit about what a “normal” cholesterol would be, and what do anthropological studies from various traditional cultures around the world tell us about this Chris?

Chris Masterjohn: That’s a great question, I think to even ask it goes back to the idea that Weston Price put forward when he traveled around the world looking at traditional healthy peoples. He was looking at tooth decay and he was saying everyone in this society basically has degenerating teeth, I need to find people who are healthy, people who don’t have tooth decay. And he also took the idea that if we can find people who have superior development compared to what we have in our own society, then this can offer us standards of excellence. So I think we can apply the same thing to heart disease. One, we wanna find are there populations out there that don’t have heart disease and if so, what do they look like. We wanna know what they’re eating, we wanna know what they’re doing, how they’re living and we wanna know what their cholesterol levels are because maybe that can tell us something about what a normal cholesterol level is. And we wanna establish them as standards of evidence because people may say, look at people in our society and say well, anyone who lives as long as we do is gonna die of heart disease eventually cause they’re gonna die of something. If we can establish that there are people out there who are living reasonable long lives and are still free of heart disease, then we’ve established a new standard of excellence and that just provides us with the basic fact that it is possible to live a long, healthy life and be free of heart disease. And if we look around the world we see quite often researchers have documented that with the nutritional transition to modern diets rich in refined foods, we clearly see this increase in degenerative diseases including heart disease and in many cases there’s been at least some investigation showing that traditional peoples before this transition to refined foods seem to have either a low rate of heart disease or freedom from heart disease.

Now I think among the groups that I’ve seen studied so far, it seems that two really stand out in terms of the extent to which they were investigated and those are the Masai and the Kitavans. I think each of these groups of people was studied quite intensively and what’s particularly amazing about them is that they have very different cholesterol levels when you look at them. The Masai for example, are a pastoralist, or cattle herding tribe who occupy a piece of land that crosses the border of Tanzania and Kenya in east Africa. They traditionally raise cattle for subsistence, to eat the meat, drink the milk and the other products that come from them, and also to trade for other products. So they have a diverse diet that varies through the seasons of the year and that also varies year to year according to economic times, because they’ll trade with other groups when their own supply of food is low or other groups are particularly wealthy. At other times they might have just tons and tons of milk and they might focus mostly on consuming the milk. In any case, the Masai have very low cholesterol levels, some of the lowest in the world and a number of groups had studied them in the 1960s and showed that the men tended to have cholesterol levels between 130-135 mg/dl, which is by our standards we would say that’s quite low. The women had somewhat higher cholesterol levels of about 145, and these would tend to rise with age maybe to 170 mg/dl in their 40s and then drop off a little bit as they grew older. It also seemed to rise quite a bit in the 3rd trimester of pregnancy, at least according to one study. Women who were in their 3rd trimester of pregnancy had their cholesterol levels go up to 205 mg/dl. But on the whole they had very low levels of cholesterol with a population mean of around 130-140, and their LDL:HDL cholesterol ratio was about 2. So that’s considered quite good, even by American standards. The medical establishment in our society would love the Masai because they seem to support the lipid hypothesis. They have very low or no rate of heart disease and they have very low cholesterol levels.

But if we look at the Kitavans who live in the Pacific islands and are horticulturalists, we see something very different. This group is living off of a little bit of fish, a little bit of coconut, a lot of tubers, a little bit of fruit. They have a very low fat intake, very intake of saturated fat from coconut, and their cholesterol levels are not through the roof by our standards, but they’re much higher than the Masai. The males, for example, tend to have cholesterol levels around 180 mg/dl, the females again are a bit higher 200-210 mg/dl. Here we’re pushing over the limit of what’s considered healthy in our society, and during their 40s or 50s women might see cholesterol levels rise to about 250 mg/dl and then settle off a little bit. A lot of the Kitavans smoke, and their LDL:HDL cholesterol ratio is 3.3 among the smokers and 2.5 among the non-smokers. And we also have triglyceride information from them, tends to be around 100-110 mg/dl. Now the Kitavans have been investigated very extensively, there are some other people in the Pacific islands who we’ve had smaller investigations that seem to indicate that they’re free of heart disease but they’re really too small to say definitively.

Nevertheless, on some of these islands we see even higher cholesterol levels traditionally. If we compare Puka-Puka and Tokelau, Polynesians who also occupy Pacific islands, the Puka-Pukans have a high intake of starches and other carbohydrates, and a fairly meaningful intake of coconut. On Tokelau they have a much higher intake of coconut. And we see on Puka-Puka we have men going from cholesterol levels of around 150-180 with age, but the women going from about 170-190 with age. But if we compare similar people eating more coconut, who also seem to be free of heart disease we see men with cholesterol levels going 180-220 over their lifespans and women going from 200-245 over their lifespans. So if we look at these populations I would say we have a range. I’m not satisfied with the idea that low cholesterol is intrinsically unhealthy, I’m willing to consider it, but I would say that the Masai should constitute the low range of what we might say is possibly healthy, and the Kitavans should probably serve as our high range. I think we could probably say that anything between maybe 140-220 maybe going a little bit higher to 250, might constitute what seems to be normal. And I would caution that the Masai, we don’t know exactly why their cholesterol levels are so low but Paul Jaminet’s been doing a series on the role of infectious diseases and we should note that infectious diseases are quite common in Africa so that might play a role. So it might give us more comfort to say maybe a little bit higher than that 160 or 180, but still we don’t really see healthy populations going through the roof in the high 200s or over 300. That seems to constitute what we can say is normal.

Chris Kresser: And it does depend, as we’ve been discussing I think somewhat on the context right Chris? I mean someone could have a cholesterol of 200 but could relatively unhealthy and at risk for heart disease whereas someone else perhaps has a cholesterol of 220-230 and they may be at still relatively low risk of heart disease depending on their lifestyle and diet and several other factors so it’s not so cut and dry that if you’re in that range you get a hall pass from heart disease.

Chris Masterjohn: Absolutely, if you really want a good example, there’s this myth floating around that because the Framingham study didn’t find anyone with cholesterol levels under 150 that that’s the freedom from heart disease range. And that’s just not true. If you look at these people with the PCSK9 gene mutations who have really high LDL receptor activity there’s been one of them who’s been found who did develop heart disease and his cholesterol was somewhere around 50-60 mg/dl. But he also smoked, he had high blood pressure, he had high LPa through the roof and so on. That’s absolutely true, and we have to realize that when we look at these cholesterol levels, they’re not diagnostics.  It’s heart disease we wanna avoid, any of the mental problems, the tendency towards suicide and the anxiety that comes with low cholesterol. These are things that we wanna avoid. But we always have to remember that there can be many things that lower cholesterol and many things that raise cholesterol and some of those things can be good and some of them bad. If we’re lowering cholesterol because we’re clearing it in to an atherosclerotic plaque, that’s clearly bad. If we’re lowering cholesterol because we’re converting it into sex hormones and bile acids and things that increase our fertility, virility, strength, and digestion and all these positive things then it’s clearly good to lower cholesterol. But if it’s low because we’re not making it, then we don’t have those substances that we need to make all those good things so that’s clearly bad. So we can never judge by the amount of cholesterol in the blood alone, but we have to use it perhaps as a clue to try to understand, with further investigation what’s happening in the body.

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Chris Kresser: So Chris, we talked a little bit on the last show about the difference in particle size, small dense LDL particles vs large buoyant LDL particles and what the relevance of that is  to cardiovascular disease risk. As you know there’s these tests out there like the VAP test or the NMR test to measure particle size and early on in my practice I was using these tests to try to get an idea of particle size but then I read several papers which suggested that these tests might not be as accurate as they’re made out to be and I think I sent you some of those papers, so what have we learned in the last few years about the accuracy of these particle size tests?

Chris Masterjohn: Well what I learned Chris, from the papers that you sent me is that if I wanna have pattern A large, fluffy LDL particles, then the best thing that I can do is not change my diet but it would simply be to measure my LDL particle size by tube gel electrophoresis, because 80% of people who measure their particle size by tube gel electrophoresis are classified as pattern A, whereas only 8% of people who use the VAP test are classified as pattern A. So the best thing that you can do to give yourself pattern A is to avoid using the VAP test number one, number two if you can really avoid NMR or gradient gel electrophoresis and go for tube gel electrophoresis that’s really your best bet.

I think the point that this is raising is there’s a lot of disagreement between these different tests. And until we get the science to the point where we can actually agree on the particle size, on what test we use, on what standards we use to classify someone as having this or that particle size or this or that size distribution, I really don’t think we’re at the point yet where we should be ordering these tests for everyone and telling them to change their diet or to do this or that thing in order to alter their particle size. But I think this goes back to a more fundamental question which is, why do we even care about the particle size in the first place. And I think we need to look at the foundation for that hypothesis. So the main reason that this came to the fore was because there were some early studies, first there were retrospective studies meaning looking at people who already had heart disease and just seeing what their particle sizes were, and we saw that people who had the larger particle sizes seemed to have a much lower prevalence of heart disease. Now this is a good observation for generating hypotheses about what the role of these different particle sizes of LDL might play in cardiovascular disease risk. But to simply have a hypothesis doesn’t really cut it, we wanna really understand whether we’re actually diagnosing something, or if we’re not diagnosing something are we getting a metabolic clue, are we helping ourselves to understand what’s going on in this person’s body or are we not. Now if we wanna argue that the small dense LDL is associated with cardiovascular disease, the first thing we would wanna do is verify that it’s a predictor in prospective studies. In other words if we measure people’s particle size now, can we predict whether they develop heart disease in the future. And even these studies have led to some very, at best ambiguous results. So we had a number of these studies and most of them did show that particle size, whether measured by gradient gel electrophoresis, NMR, or in one case it was estimated by the apo B to LDL cholesterol ratio, and the logic of that test is you have one apo B protein per particle, so if you have a higher ratio of particles to cholesterol than presumably you have more small dense particles rather than fewer large buoyant particles. Now all of these different methods did have some success in predicting cardiovascular disease, but in most of these studies when they were adjusted for traditional risk factors, the predictive power was mostly lost.

Perhaps the most successful study I’ve seen was the Quebec Cardiovascular Study where they used gradient gel electrophoresis. And they found that if they looked at the distribution of particle size, it was an independent predictor of heart disease risk. But a number of other studies that came after that failed to bear this out. So the Stanford Five City Project, for example, showed that particle size was useful but once they adjusted for the total:HDL cholesterol ratio, it wasn’t useful anymore. The Physicians Health Study showed that particle size was useful but once they adjusted for triglycerides and total cholesterol it wasn’t useful anymore. The epic Norfolk study measured by NMR, they found that particle size was useful but they found that particle number was much more useful. But when they adjusted particle number for HDL cholesterol and triglycerides once again its usefulness was very questionable. And there was another study, the AMORIS study, the apolipoprotein related mortality risk study, and that looked at particle size estimated by the apo B to LDL cholesterol ratio and once again it seemed useful at first but once they adjusted it to triglycerides or to apo B it lost its usefulness and then finally in the womens health study they also looked at particle size with NMR and once again it lost its usefulness after adjusting for the total:HDL cholesterol ratio.

Chris Kresser: Chris, at the risk of stating something obvious here, how much can we rely on these studies since they’re all using methodologies that we’ve just established are totally in disagreement with one another and not reliable?

Chris Masterjohn: Well, right this is the thing. If we can’t agree on how to quantify the particle size, then we can’t necessarily agree that these studies are showing that particle size isn’t useful. But at the same time, what meaningfulness does that question have to the average person that’s walking to the office and wants a test. Are you gonna get into some really esoteric academic argument about, this test isn’t going to do anything for you but theoretically it could be an imperfect measurement of something out there that does have meaning for you. I mean where are you getting with that? Nowhere.

Chris Kresser: We can neither prove that particle size is not an issue nor prove that it is an issue with the current test because all of that rests on methodology that hasn’t been standardized or agreed upon.

Chris Masterjohn: Exactly, so this is where particle size is useful. The studies that have somewhat ambivalently but nevertheless shown some relationship between particle size and cardiovascular disease risk have left us with several hypotheses that are worthy of investigation. One is that small dense LDL is more likely to oxidize and thereby contribute to plaque development. Another is that it’s more likely to pass through the endothelium and thereby oxidize because it’s behind the blood vessel wall and contribute to plaque development. Another is that it’s more likely to get stuck behind the blood vessel wall and thus contribute to plaque development. And my perspective is, I’ve pointed this out in several places, and I believe I mentioned it in our previous interview, it could also be seen as a marker for poor LDL receptor activity and LDL oxidation because what happens when LDL hangs out in the blood. Well it becomes small and dense because it’s metabolized by a number of different enzymes that make it small and dense and because when it oxidizes, it becomes even more small and dense. So here we have about four different hypotheses that are worthy of investigation, none of which have been confirmed. So it’s highly questionable that we should be going around batting people over the head and say  make sure you do this, this, this, and this, to modify your particle size.

Chris Kresser: Right, I’ve seen some people, some patients who’ve come to me and also chatter on the internet on my blog and other blogs going to extreme lengths  to try to adjust there ratio as measured by a VAP test or NMR test.

Chris Masterjohn: Yeah absolutely, I will say this. I mentioned as I ran down this list of studies, that the traditional risk factors like triglycerides and total:HDL cholesterol ratio, were the factors that seemed to mitigate the usefulness of these tests, which brings us back to the question, are these tests any useful. Should you measure your total cholesterol or your HDL cholesterol. And I will say that we have many more studies addressing this topic so we’re able to amass a much larger data set and better answer the question. And we also have some, not that it’s without questions, but we have some better agreement on what tests to use to measure these things. And there is good data suggesting that there is, at a population level in the general population, there is predictive value to some of these blood lipid markers and that the best of them is the total:HDL cholesterol ratio. So if we look for example at two meta analyses that were published in the last few years, one was the emerging risk factors collaboration, and that was published in the Journal of the American Medical Association in 2009. And they showed that fasting triglycerides, HDL cholesterol, and non-HDL cholesterol were all useful predictors, but if they adjusted triglycerides for the other predictors triglycerides lost their significance. But if they adjusted HDL and non-HDL cholesterol for triglycerides, non-HDL and HDL cholesterol persisted in their predictive power. And there was another study, the perspective studies collaboration which pooled together results form 61 studies with 900,000 participants that was published in the Lancet in 2007 and they found that if you looked at total cholesterol, HDL cholesterol, or LDL cholesterol or any of the ratios, it was the total:HDL cholesterol ratio that really stood out as the best predictor. Now what can we learn from that. Well, can we use the total: HDL cholesterol ratio as a diagnosis? No, a high ratio is not a disease, a low ratio is not a disease. Can we use it to predict risk? Yes we can at a population level, not at an individual level. I think it’s a logical fallacy to say a population with this mean has such and such a risk therefore if you have that same value, you have such and such a risk. I think that’s bogus reasoning.

Chris Kresser: And it comes up a lot in a lot of different markers. The hemoglobin A1c is another example of that it’s really useful on a population level but it’s not so useful individually because there’s so many different markers that can effect red blood cell turnover which is part of that formula and so it’s really not that useful for individuals.

Chris Masterjohn: Absolutely, there are many things that can effect the total:HDL cholesterol ratio. But does that mean it has no usefulness. Can we use it in some way as a metabolic clue. And I think that we can. But I don’t think that it should ever be used without further investigation to see if that ratio goes out of whack, why is it going out of whack. And the reason that I think it’s valuable is especially because, you recently commented for example, I think this was on twitter, you were talking about people, you see so many people with low thyroid levels and Emily Deans was saying she doesn’t see that many people with low thyroid levels. So why is this, well you say you’re getting a lot of these people who go all these different places and finally come to you because no one else is helping them. So we have to keep in mind that if we’re trying to reach out to people who are seeing mainstream doctors for a lot of those people these are the only things that they’re testing. So when they go to the doctor, the doctor’s not measuring their hepatic triglycerides, the doctor’s not measuring their free T3. I’ve gone to a doctor and said can you give me a full thyroid panel with TSH, free T3, free T4 he says sure. And then the test comes back and it has TSH on it. So your average person going to the doctor, this is what they’re getting. So when they go onto some internet forum and their total cholesterol has gone up to 350 and their HDL cholesterol is really low and they get a bunch of people saying oh these things don’t have anything to do with anything they’re not causal factors just ignore it, that might be fine advice if their doctor had also measured this battery of things that you measure when patients walk into your office, but they’re not. So for those people I think we need to say this needs some follow up. Let’s see if this is going out of whack because of your thyroid, let’s see if this is going out of whack because you have insulin resistance, you have fatty liver, let’s try to look at these further issues, that’s where I think the blood lipids come into usefulness.

Chris Kresser: Yeah. I agree completely and my standard answer and I imagine it’s similar to yours, when someone says is my cholesterol a problem I say I don’t know. Or maybe or it depends. And it definitely requires a lot more investigation and as you pointed out unfortunately that’s rarely done in the conventional model. It’s high cholesterol you get a statin, just like when it’s high TSH or low T3 you get thyroid hormone without looking into the mechanism.

Chris Masterjohn: Exactly so I think those of us who are in the know, who understand that there’s a lot more to the picture, our response has to be exactly what you said, I don’t know let’s look at the big picture.

Chris Kresser: So Chris, this question that just comes up all the time in the blogosphere, it’s this question of why is my cholesterol so high after adopting a nutrient dense, whether we’re talking about a Paleo or a Weston A Price style diet that’s higher in saturated fat. There’s been a lot written about that Paul Jaminet in fact just wrote an article about this question yesterday and he’s been blogging about it recently. You’ve written about it, can we do a little summary of the possible factors there and as a corollary is it something that people need to be concerned about when their LDL cholesterol goes up on this type of diet.

Chris Masterjohn: Absolutely, but first let’s outline how do we know that it’s actually gone up. Because quite often there are some confounding factors, or people don’t realize how much they can expect these values to fluctuate just on a regular basis. So for example let’s say I went and got my cholesterol tested once while I was on diet A, and it’s 180 mg/dl. And I get it tested once when I’m on diet B and it’s 200 mg/dl. Can I conclude that it’s gone up since I’ve been on diet B. And the answer is an emphatic no, you cannot conclude that it’s gone up. And this is the reason, there is very large fluctuation in total cholesterol, LDL cholesterol, HDL cholesterol, the ratio, and triglyceride levels. Just on a week to week or month to month basis without making any dietary changes. And studies that have been done to try to address the question, if we keep diet and lifestyle constant how much can we expect this to vary if we make these measurements several times over the course of several months. And these are basic answers, we can expect a single person to have a standard deviation in their total cholesterol of about 17 mg/dl. Now what does this mean, well it means that if we haven’t done anything to assess for example, my individual variation over time, we should assume that if you measured my cholesterol 100 times you’d find some true mean, some true average cholesterol level. But we could expect without any changes it to go up about 2 standard deviations so about 35 mg/dl, or down about 35 mg/dl for no reason at all.

Chris Kresser: That is a huge range. That could be the difference between statin or no statin just depending on what day somebody chose to go into the doctor’s office.

Chris Masterjohn: Oh absolutely. Exactly, so when you go into the doctor’s office and your LDL cholesterol has gone up 30 mg/dl and your doctor days oh no your cholesterol’s gone up so much you need Lipitor, the best answer for that is not ‘yeah but what’s my particle size, I bet it’s large and fluffy’, the best answer for that is, did you know that the standard deviation of the intra-individual variation in one person can be 17 mg/dl and that this is within the range and you do not have 95% confidence that my cholesterol level has even increased since the last time I came up here. I think you should go look at this, this, and this study.

So here’s the general rule. If you’ve only measured it two times, you should expect to see an increase or a decrease greater than 35 mg/dl before you can be 95% confident that your cholesterol has increased or decreased. You should expect your HDL cholesterol to go up either 9 or 10 mg/dl or down 9 or 10 mg/dl before you can say with 95% that it’s increased or decreased. You can expect your LDL cholesterol to go up either 30 mg/dl or down 30 mg/dl before you can conclude that it’s different. If you’re looking at the ratio you should expect the ratio of LDL:HDL cholesterol or total:HDL cholesterol to go up by 0.8 or down by 0.8 before you can conclude it’s changed. And you should expect your triglycerides to go up by at least 40 mg/dl or down by at least 40 mg/dl before you can conclude that they’ve changed.

Chris Kresser: Wow, I mean talk about problems with testing. I have a little n=1 story about this cause I recently, being a new dad, decided to get life insurance. I had to take this test of my lipids, I new I wasn’t obviously gonna be able to convince the insurance company, no, no really, if my cholesterol’s a little high it’s not a problem, it’s all about oxidized LDL, that obviously wasn’t gonna happen. And so being a clinician I ordered some tests for myself as the time was approaching to see where I was at, cause the better the numbers are the better the rate, and I was buying a ten year policy. The first time I tested my cholesterol it was 185 I think, my total, which was significantly lower than it was the last time I tested it six months ago. And I thought okay that’s fine and I tested it again a couple of weeks before the test and it was 220, and I thought my rate’s gonna go up. And I didn’t make any changes because I was a aware of this research too. And then I tested it the day before the test and it was 193 and then I took the test the very next day and they just mailed me the results yesterday and it was 205 which incidentally was under their cutoff so I got the good rate but that’s just a single person example and that was over only a four week period.

Chris Masterjohn: Yeah, absolutely that’s the kind of variation you can expect for biological reasons. I’m citing these values on variation by the way, from studies where they used the same method at the same lab from these people. Where they analyzed the samples in duplicate showing that the actual variation due to the lab assay was very small, like 1-2%, and that most of this variation is biological. In order to conclude that it’s even changed outside of your normal variation when everything’s staying the same, those are the large kind of values that you need. Now the second thing you need, the one exception to this by the way, would be if you had an average while you were on one diet and you had measured it 3 or 4 or 5 or 6 times, and then you do the same on a new diet, then you have a sense of your own variation so you can compare them. But in the absence of that, you just measured a couple times, once on an old diet once on a new diet, you need really large changes to conclude something’s different. Now the second thing is, I often get these questions from people who say I went on this diet and my triglycerides went through the roof, my this or that went through the roof. And I say, one of the first questions I’ll ask these people is, did your weight change. And quite often they say oh yeah that’s true. And here’s the thing, there’s really no good research I’ve seen so far about the effects of weight loss, fasting, and caloric reduction, on blood lipids. There are a lot of fairly poorly designed studies, and I’ve reviewed a lot of them, and they’re at wild conflict with one another. But this is what I’ve basically concluded as tentative working hypothesis, if you are obese or overweight and you normalize your weight and normalize all your metabolic parameters, you should expect in the long term, after your weight has stabilized, your blood lipids to mostly improve according to the conventional paradigm of risk factors.

But in the meantime what happens, triglycerides are especially sensitive to fasting, when you eat a meal your triglycerides are gonna go up, your triglycerides are always going to be lowest when you’ve been fasting in the morning so especially with triglycerides you always wanna measure them the same time of day and always in the same amount of fasting since your last meal so that’s another confounder. But what happens when someone fasts for a long period of time to their triglycerides well the answer is it depends. Usually, because you don’t have food in your system  your triglycerides are gonna get cleared over the course of a day of fasting or so, but what also happens is you need to start burning your own energy stores. So when you start to shift towards burning fat from your adipose stores you start releasing free fatty acids into the blood. Now these free fatty acids basically have three important fates. One is they go to the liver, the liver burns them for energy, the liver makes ketones so the rest of your body can burn them for energy. But two other things happen in the liver, one those free fatty acids can interfere with certain signals for example they interfere with thyroid hormone signaling, and as we know especially in the blogosphere recently and as we talked about last time, interfering with thyroid signaling itself can affect blood lipids. But here’s the other thing, if the liver’s capacity to burn the fatty acids for energy is overwhelmed, the liver makes triglycerides out of them and sends the triglycerides into the blood. So one person who has a very high capacity to burn fatty acids for energy might see their triglycerides go down as they’re losing weight, but another person who’s releasing more triglycerides from their adipose tissue than their liver can handle might see their triglycerides go up as they lose weight.

Danny: What type of fatty acids were those that inhibited thyroid function?

Chris Kresser: Free fatty acids.

Chris Masterjohn: There’s good preliminary evidence that any unsaturated free fatty acids are quite good at inhibiting thyroid function. And it’s not just PUFAs, even oleic acid is pretty good at it, and there’s really nothing you can do to suppress oleic acid in your body cause you can make it yourself. PUFAs also play a role it’s just that you have a lot more oleic acid. So basically any release of free fatty acids is probably going to inhibit thyroid signaling and the best evidence for this is at the level of thyroid binding to the nuclear receptor and then binding to DNA. It seems that the concentrations of free fatty acids do get high enough in the nucleus of the cell to inhibit signaling there and that will not be reflected by free T3 levels in the blood or anything like that. So it would be very difficult to detect it clinically, but it’s probably a fact during weight loss or during any kind of dieting that leads to large increases in free fatty acids.

So here’s the thing, many people when they lose weight will see their triglycerides go up. They may see their cholesterol go up and so on too, but it’s all highly dependent on the person. So someone who has very good micronutrient status, all the micronutrients that they need to burn energy, has good thyroid hormone status, has all the things that we would expect to promote burning energy at the liver, this person might just burn that energy really efficiently and their blood lipids might improve the whole time. Someone else who’s losing adipose mass might see quite different results. They may develop fatty liver if they don’t have enough choline to get rid of the fatty acids that they can’t burn so they get stuck in the liver. But if they have enough choline, for example if they’re on a paleo diet with a lot of liver and egg yolks, so they’re getting lots of choline but they’re not getting enough of some other nutrient or some other factor that’s needed to burn that energy, they’re gonna see their triglycerides go up and they might see their cholesterol and other things go up as well.

So this would be my advice first make sure that the difference is large enough to say it’s actually increased. Second, if you’ve been losing weight don’t even look at your blood lipids until your weight is stable. If you’re obese and overweight, normalize your metabolism, normalize your weight, normalize your body fat, wait til it’s stable for a few months and then test your blood lipids. And if it’s triglycerides make sure it’s fasting, make sure it’s been the same length of time since your last meal and those things. Only then should we even begin to say okay there is an increase or there is a decrease that’s  meaningful.

Chris Kresser: Chris, thank you so much we’re gonna have to have you back for part three it looks like cause we’re out of time for today. But we’re so grateful to have you on the show it’s really exciting to get all of this super current information. I tweeted this out right before we started the show, I honestly believe that if people listen to part 1 and part 2 of this podcast about cholesterol they’re gonna know more about it than probably 99% of doctors at this point.

Chris Masterjohn: Yeah well I think this was a great show and I think this is the testing blood lipids show and if we have a part 3, then part 3 can be if you have all of those factors that convince you your blood lipids are actually changed what do we do about it.

Chris Kresser: That’s the cliffhanger. Sorry to leave you hanging folks but this is obviously as not as simple as it’s made out to be in the conventional paradigm. We’ll definitely have Chris back if he’ll join us again.

Chris Masterjohn: Absolutely thank you so much Chris and thank you so much Danny it was great to be here.

Chris Kresser: You’re welcome, Danny take it away.

Danny: That’s gonna bring us to the end of this week’s episode. Chris Masterjohn where can we find more of your work on the internet this week?

Chris Masterjohn: You can find me at cholesterol-and-health.com and my blog the daily lipid, and there I also post all the links to my mother natured obeyed blog over at WestonAPrice.org and you can also follow my on facebook and twitter.

Danny: Mr. Kresser, same question to you.

Chris Kresser: Same place, we’re at Chriskresser.com now, the Healthy Skeptic is retired, is no longer. It’s all there at ChrisKresser.com and then join me at Facebook, Twitter. I’m writing a series I just published the first article yesterday on low T3 syndrome. Some of this is gonna dovetail what we’re talking about with Chris on the show today about cholesterol. If you’ve got low T3 but your TSH is either normal or even low, which is not the typical hypothyroid presentation, you might wanna check this series out. And then I’m still finishing up the series on natural childbirth. I’ve got one more article to write on the potential side effects and complications of cesarian sections. So look for that in the next week or so, that’ll wrap that series up.

Danny: You can find all of Chris’ work at Chriskresser.com. You can find me at Dannyroddy.com. Keep sending us your questions at thehealthyskeptic.org using the podcast submission link. If you enjoy listening to this podcast head over to iTunes and leave us a review. Thank you for listening and thank you for your support.

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Join the conversation

  1. Hi Chris and Chris. Thanks so much for putting this together. There is so much confusion out there on this topic and it’s nice to have people digging into the nitty gritty.

    As you both know, I’ve been around for a bit. I’m all up in the Paleo Blogosphere and understand what it really means to eat whole healthy nutrient dense foods. It’s what I do.

    Chris Masterjohn, you chimed in on my VAP results from July with some great insight that was much appreciated by many. Given my situation, I’ve become somewhat of a poster boy for a person who has gone all in with adopted a Paleo/WAPF style diet and seen some concerning changes to my blood lipids.

    Well.. I just got tested again for a host of markers last Friday. Much of the panel came back with what I would consider pretty positive results, which was encouraging to me. But this morning, I received the VAP results back from my Doc, and I gotta say, it was tough to see.

    I posted my labs on PaleoHacks and they are ‘hacking’ away to try to make sense of this.


    Also, I was glad to hear you mention in the end of this podcast about people losing weight not getting wrapped up in lipid numbers until their desired weight is reached. I posted this other question on PH earlier today before hearing your podcast tonight. If you want a prime example question related to exactly what you addressed there, have a look at this:


    Here’s the deal. I love this community. I think you all are some of the brightest folks in the health world. I’m all about it. I just don’t want to be irresponsible or flippant with my personal situation, and coupling what I’ve learned about how to eat well with my results leaves me quite confused.

    My question for you is… if you were me… would you be concerned to see that VAP come back with your name on it? and if yes, what would you do?

    As always, any insight into this is much appreciated, by me of course, by I think at this point, by many others as well.


  2. Heh, is oxLDL collapsing the economy or are you that musician guy? Chris Martenson, Chris Masterson…Matterson? Googling you is hard!

    • Funny thing is, I like Chris Martenson a lot too. He might be the Chris Masterjohn of energy, environmental and economic analysis.

  3. Excellent podcast guys.
    Chris M – I have a curvy question – Is there any method you know of, to temporarily reduce LDL? swing it towards the lower end of the 2 S.D that you mention? It’s not that I am worried myself perse, but just to get some “desirable” numbers on my test and to get others off my back! (mainly work, as it’s on annual medical thing) LDL has been creeping up from 130 to 140, which I am not so worried about in the general scheme of things.
    HDL is 60-ish, Trig mid 60’s.


    • Hi Dean,

      Maybe you could try a soluble fiber like psyllium. You could, of course, take a natural statin like red yeast rice, if you feel it’s really worth it. I’d take a formula that has CoQ10 in it though if you’re going to go that route.


  4. Thanks for this podcast. Very clear and hit a number of important nails on the head. In particular, it was good to hear Chris M discuss the fallibility of testing for lipids. What we usually find, with the annual cholesterol check, is a mere snapshot in time. What we want to know is whether the number is trending or moving in a range. In most cases lipid numbers will move in a range. It would be more meaningful to represent lipids as a range over a period of time, such as Chris K’s testing over a week or two, rather than a single snapshot in time.

    Further confusing the issue is the margin of error in measurement. During a recent weekly lipid testing mania, my lab technician performed two (and occasionally three) tests on the same sample. Variations were as much as 10% between the test results, sometimes greater.

    Tendency to form wide ranges and margins of error in testing limit the value of pinning a single cholesterol number on a person. The broad range of optimal lipid values in the O Primitivo study of 164 countries, as cited on Paul Jaminet’s site, reflects the fact that normal cholesterol moves in a much wider range than conventional medicine would allow.

    Looking forward to Part 3!

    • Hi Gregory,

      Excellent point. Population variation in this sense, is a fallacy. Not because there isn’t any, but because estimating it based on a single measurement incorporates the intraindividual variation.

      I’m looking forward to it too!


  5. Chris^2 – great podcast. Looking forward to Part 3. I have a friend that recently called me very concerned about her increased lipid levels after adopting a Paleo diet and so these podcasts are timely for her. Thanks so much!!!


  6. Steve,
    Optimal thyroid would be in the upper half of the range. Your free T3 is low.
    You would get more assistance from the yahoo rT3 group.

  7. Great podcast, wondering if one of you could post the references mentioned, particularly the ones describing different results on nmr vs vap?

  8. Seems everything comes in cycles..

    First it was Ancel Keys on why saturated fat and dietary cholesterol is bad for you.. but then the Atkins Low Carbers, strike back…

    Then Denise Minger goes at it with the China Syndrome book and documentaries

    (Even fructose got into the mix when Alan Aragon and Robert Lustig got into a heated debate!)

    And now of course the battle continues with…
    The Gary Taubes / Tom Naughton / Paleo / Primal / Diet de-jour vs Stephen Guyenet , James Krieger, Chris MasterJohn , etc

    It seems obesity, like gravity, even after decades+ of research, we understand the effects, but have little understanding on what makes it work.

    At heart of the (current) controversy, seems to be whether or not a carb-rich diet causes obesity and that increase in fat storage is directly attributed to an elevated insulin response…

    Chris: An interview with bloggers like CarbSane (NEFA fame) or Ned Kock would be great! They seem to be have balanced thinking!

  9. Excellent podcast, gents. I’ve always enjoyed Chris Masterjohn’s work; in both his writing and public speaking he excels at clearly explaining complex mechanisms. Definitely bring him back for part 3.

  10. When you guys talk about optimizing thyroid what do you mean? For ex, my FreeT3 was 2.6(range of2.3-4.2) and Free T4 was 1.24( rnage of .89-1.76). TSH was 1.7. My understanding is that thyroid is dynamic and can fluctuate (diet ,stress could affect it) like you have pointed out with cholesterol. Based on my numbers would would optimizing thyroid for me really make much of a difference in LDL receptor activity? What would you recommend for investigation if you think there are things to do with my thyroid that would meaningfully increase the LDL receptor activity? I am searching for answers as i find my cholesterol and particle levels vary substantially with diet, but there is consistency in putting out tons of particles( ie with LDL of 99 i put out 1600 particles; when LDL was 185 i had particles of 2100). If i try a statin and zetia, the LDL falls to 55 and particle count to 640. Family history of heart attack and i am Apo E3/3 which surprised me. Vitmain D has ranged from 40’s to 60’s; weight is 142 and height of 5’6″. I am almost concluding that i may be one of the few who needs a statin since i have CAD via calcium scan, but IMT is normal for my age, 60.
    Very nice to see smart people like the both of questioning convention and yet maintain open minds. Something clearly missing in dialogue through all parts of our society.
    Thanks much

    • That’s a great example of what I was talking about. There was no control group and the order of the three phases were not randomized. The study is essentially a large-sized anecdote.


      • Just a quick comment. If it’s the Varady study you are both referring to, then the study subjects acted as their own control in the initial two weeks of the study. This is quite legitimate in clinical research. And the use of control groups is not always necessary to draw hard conclusions if the effects you are testing are well-known (if it is an extension trial, for example). Plus, the fact that the study phases were not randomized, which is a very, very minor point, does not invalidate the study. This is actually an informative study. Not observational or anecdotal. I don’t understand why you dismiss it so offhandedly, Chris.

        • Hi Stipetic,

          I disagree with you. It is of course quite possible to publish a paper like this and indeed it is done quite often, but randomization is the key element that allows legitimate causal inferences whether subjects act as their own controls or whether some subjects act as controls for others. That you consider this a “very minor point” indicates we have very different philosophical approaches to experimental design. I’d be happy to discuss them further if you’d like.


          • Randomisation of subjects is crucial–we do it in every study we conduct. That’s not the issue here. The Varady study had only one group of subjects (as far as I can tell from the abstract), so randomization was not possible. Now that I’ve reread your original comment, I’m not sure what type of randomisation you were talking about. Stage order randomisation? Study designs are usually not randomised (they are typically templates, ie. 2-period, 2-sequence, crossover, etc). Study stages are not randomised, subjects are. So, I don’t believe it’s philosophical at all and there really is no need to discuss this further. I was just making a point about how I find some people are misinterpreting the the presence or absence of a control group since I design study trials for a living (and the Varady study did not fail my whiff test). Everyone is free to accept or reject what I say for whatever reasons.

            • Hi Stipetic,

              I agree that it is subjects we randomize and not study designs. A study design, however, needs to have an element of randomization in order to draw causal inferences. If it doesn’t have one, it’s not illegitimate, but it is observational and the inferences one can make are different. In a crossover design, one would randomize the subjects to undergo one of two or more orders for the trial periods. I would call that randomized order for simplicity, but technically it is the subjects who are randomized.


  11. Enjoyed the podcast! Looking forward to part 3. I had a major bump in TC & LDL from my historical baselines after adopting a paleo diet.

    I did lose some weight, not a crazy amount, when I started eating paleo lowish carb. This has got me thinking though, about the other changes that occurred when I changed from my SAD diet to a paleo diet. I started taking a table spoon or two of carlson’s fish oil every day for the first month then titrated down to a teaspoon a day. I also stopped taking citrucel/metmuscil which I had taken daily for about the last 5 years. I wonder if those things could also be factors?

    • Citrucel maybe but likely not if it’s all cellulose, as it is mostly soluble fibers that lower cholesterol. Metamucil, quite certainly, as psyllium has been demonstrated to lower cholesterol, probably by a mechanism similar to cholestyramine — binding bile acids and sterols in the intestine and increasing liver LDL receptor as the liver attempt to make up for the lost cholesterol and bile acids.


      • I realize I’m several months late and Chris may not be checking comments on this page any longer, but hopefully.
        In regards to psyllium – my husband had his cholesterol checked for the first time since adopting a paleo diet. The LDL number is 182, which doctor was very concerned about. (HDL 62, TG 76). Doctor advised he take psyllium to lower the number. Is there any point in taking psyllium or would this actually do more harm? I’m not so worried about his numbers, but he would like to get the doctor “off his back” so to speak.

        • Hi Pam,

          I don’t check the comments but I’m subscribed my email. Ah the wonders of the internet. 🙂

          Psyillium will lower his cholesterol, assuming he behaves according to the group means of previous studies. The mechanism is not totally worked out. I suspect that it acts similarly to cholestyramine, by binding bile acids and diverting cholesterol into the bile acid synthesis pathway. In all likelihood, it probably promotes the excretion of various toxins, so that is another benefit. If it is fermented to short-chain fatty acids it might also lower cholesterol by some other means when these are absorbed. On the whole, I think if it doesn’t seem to cause gastrointestinal discomfort, it’s likely to be somewhere between harmless and beneficial, and it will probably help get the doctor off his back.

          Hope that helps,

  12. I’m still searching for an answer about my cholesterol numbers… My total cholesterol is about 400, and my LDL is 300… I know that is extremely high, but every other predictor of heart disease is excellent: HDL is 100, triglycerides 52, CRP 0.26, blood pressure 110/70, etc. Should I be worried?

      • I’ve looked into it a little, but I never know who to trust on the subject. My doctor seems convinced that I’ll have a heart attack in my 30’s if I don’t get on statins, but that can’t be true right?

        • I would try to find genetic testing. You’re interested in the cause — so I would attempt to get the cause tested. Then you can understand better whether you should worry, how much, and what you should do about it.


            • Hi Rob,

              I think it could be useful for explaining blood lipids in some cases, but not so sure about the diets. I’ll try to look into it, think about it, and write about it more in the future. Thanks for the suggestion.


        • I agree with Chris. Get the genetic test for FH, then you’ll have a better sense of whether this is a functional or genetic problem.

          • Awesome, thanks so much Chris and Chris for your help, I really appreciate it. Is this genetic test something I can get from my conventional doctor?

            • Yes, if he’ll order it for you. It’s called the Familial Hypercholesterolemia Screen, and it’s test #368600 with Labcorp.

    • Brendan,

      Numbers like that can be indicative of heterozygous familial hypercholesterolemia. As Chris mentioned in the last podcast, in the general population there is a higher risk of CVD mortality with FH. This is likely due to increased risk of oxidation of LDL because of poorly functioning LDL receptors. My approach with FH is to optimize thyroid function (because T3 is required to activate the LDL receptor) and reduce risk factors associated with oxidative damage to the greatest extent possible. Unfortunately, we do not have studies of CVD/mortality risk with FH people doing all of this stuff, but I suspect if we did, their risk would be lower than FH people that aren’t. Interesting side note is that one reasons statins work (in the small percentage of the population they do work for) is because they activate the LDL receptor.

  13. “- why do some people have high cholesterol (TC & LDL) after adopting a Paleo/WAPF diet? is this something to be concerned about?”

    It seems like you didn’t actually answer this question – or did I miss it? Anyway, I’m dying to know the answer since this is exactly my predicament. Everything looks great except LDL is super high (~250). Haven’t lost any weight recently and am at ~15%bf. I lift weights regularly, feel fine. I have a large thyroid nodule, but my thyroid levels were normal.

    High cholesterol runs in my family while heart disease does not. The vast majority of my relatives have lived to ripe old ages. Doctor wants to put me on statins, of course.

    Awesome podcast by the way.

    • Hi Matt,

      Yes, we will get to this in part 3. Establishing how one concludes that one’s cholesterol has gone up enough to care about it took the whole of part 2. If you have abnormal thyroid anatomy, doesn’t this indicate thyroid problems are a likely culprit? I realize they are considered asymptomatic, but am somewhat skeptical. Glad you liked the podcast! Hope the next one and future blog posts of mine can help you.


      • Matt,

        I’d second Masterjohn’s thoughts! Consider also testing for apoE status. E4 alleles are associated with higher glycation susceptibility to oxidation as well as higher LDLs


        Your lipoprotein look helluva SUPER to me!

        Thyroid nodules are sometimes resultant from mineral discrepancies between utilization and environmental availability and genotypes. All the marine-based minerals are vital to our health (probably those who evolved near the shore more so, than those who evolved in mountainous-steppe areas, I hypothesize, like apo E4 carriers).

        How is your selenium status or consumption of mineral rich foods? Low selenium (esp as it relates to iodine sufficiency) may have huge factors in benign thyroid nodule development.

        Great podcast!! My favorite subject…

        Hope that helps!

      • That thyroid hormones affect LDL uptake was new information to me. I will definitely be looking into it. Should have seen the endocrinologist instead of the cardiologist in the first place.

        Looking forward to part III.

  14. The reader can look up a study on aging done by Albert Einstein College in the Journal of the American Geriatric Society Aug.2011. In the study 477 people were interviewed who were 94 to 109 years old. Most were Askenazi Jews. They asked them about diet, exercise, smoking, drinking and other factors. They also asked the participants why they thought they lived so long.

    I am not going to explain the study but what they found was that diet did not make that much difference but neither did alcohol use, diet, weight etc. Basically, if ones parents lived long, they lived long. The reason given by the participants for their long life varied.

  15. Excellent presentation: Now i understand why doctors have such a heard time and resort to statin prescriptions for patients. While measurement of Lipoproteins is inexact, i think that what is more meaningful for diagnostic purposes is not so much whether you are Pattern A or B, but what is the total particle level in relationship to the LDL. For example if you LDL is 99, which most consider good and you have particles of 1600 of which 40% are small you may have an issue to address either via diet or some other way of lowering the particle number and changing the mix. Be interested in hearing from each of Chris K and M as to their view on this. Look forward to hearing part three

    • Hi Steve,

      I think this is possible, but again, the importance of particle number and size is in its infancy right now. I think the best evidence is behind promoting rapidly clearance of lipoproteins and preventing oxidation by supporting antioxidant defense, proper endocrine signaling, and minimizing inflammation. Whether particle number or size is an independent contributor to the process rather than just an indicator that these other things have gone wrong is not at all clear to me at this point.


  16. Hello Chris. I was curious as to why protein signalling hasn’t been mentioned? It would seem that AGEs would be an issue with lipoproteins as they are with other protein signaling pathways. This leaves us with the main culprits of PUFAs (increasing rate of glycation) and overconsumption of refined sugars. This disruption of protein signalling would seem to increase time spent in circulation and thus increasing oxidation of said lipoproteins.

    • Hi Gabe,

      Well, I did mention protein signaling a little, but I was not discussing the detailed mechanisms in this podcast, but rather the questions, “what are normal blood lipids, does it matter, how do we determine if ours are abnormal? As I’ve said in recent interviews and talks, I consider “cellular miscommunication” to be key part of this. Since proteins are key communicators, this indicates a disruption in protein signaling.

      I agree that one cannot discuss the molecular mechanisms of atherosclerosis comprehensively without discussing AGEs, but I’m unsure of why you use the term “protein signaling” to describe them.

      I also agree that consumption of refined sugars and PUFAs can increase the aberrant formation of AGEs, but I’m unsure why they would be seen as more specific to this process than to anything else I’ve discussed.

      Perhaps you could elaborate.


      • From my understanding, lipoproteins serve at least a duel function (what we may know). One is as a lipid and cholesterol transporter and the other as an immune system modulator. Now, if the surface proteins are not functioning properly (via AGEs), not able to properly be recognized or interact with other cell surface proteins, then one can begin to at least imagine some ill effects resulting from this. Cholesterol “delivery” to cells would be disrupted and the lipoproteins ability to “signal” to immune cells and bind to pathogens and endotoxin would be compromised. I am just trying to make sense of it all. I almost feel like, “Why bother!” Lastly, I believe The Jaminet’s recently blogged about hunter-gatherer populations and concluded that much of the early methods for blood lipid measurements were unreliable and were higher than originally thought to be. Thank you for your response and I really appreciate all of you taking the time to communicate these issues.

        • Hi Gabe,

          I agree there is some support for a role of lipoproteins in the immune system, although I think their role in lipid transport is much more clearly laid out at this point. Either way, if AGEs modify LDL then you get a somewhat similar scenario as you get with oxidation of the lipoprotein. In either case, it is modification of protein that results in the lipoprotein being taken up into an atherosclerotic plaque. In people who are not diabetics, oxidation and nitration seem to be more important. In diabetics, AGE modification seems to be become important.

          That said, most AGEs are formed intracellularly, not in plasma. Oxidative stress causes AGE formation, and AGE formation causes oxidative stress. Intracellular AGE modification could well be contributing to oxidation of lipoproteins in plasma. So distinguishing the two reaches a level of detail that is quite beyond the scope of any of the podcasts we’ve done. When I say “degeneration of lipoproteins,” I’m just trying to paint with a broad brush the general picture of deterioration of the lipoprotein that includes oxidation, nitration, or AGE-modification of the phospholipids and protein.

          I would say, though, that AGE formation is probably a legitimate form of communication rather than an intrinsic “disruption” of communication. There is evidence for this, and I’ll write about it in future blog posts.

          I didn’t talk about any hunter-gatherers. The Masai are pastoralists and the Kitavans are horticulturalists. Neither are hunter-gatherers. When the Masai were studied, the samples were kept on dry ice and analyzed with the support of the Framingham study. So I think those numbers are probably accurate. The Kitavans were studied even more recently than the Masai.


  17. Hi, Sorry, one more question: If I had fairly high cholesterol (as tested several times with the right tests, and stable weight, and so on), and if I had an unlimited supply of free Statins, what would be wrong with taking them to lower cholesterol, presuming the drug would also lower the oxidized LDL fraction also. Just to be safe.
    Thanks, and no more questions. Promise.

    • Hi Again Gordon,

      Statins have positive effects and negative effects. If your cholesterol is out of whack (i.e. clearly out of the normal range, indicating the possibility of a metabolic issue), I think the first thing that should be done is attempt to identify the metabolic problem, and then the second thing should be to fix it if one is discovered. Since there are no metabolic problems that arise from statin deficiency, I think the better course of action is to address the root cause and use drugs when other approaches have been exhausted.


  18. Hi, My question is this: Is it not true that only a certain percentage (fairly low?) of cholesterol comes from diet? If so, what role, if any, do our diets play in raising or lowering cholesterol?

    • Hi Gordon,

      Diet plays a role in a number of ways, but I think it is wrong to attempt to modify the concentration of cholesterol in the blood directly through diet as some of the dietary factors that lower cholesterol are not good for you, and others are good for you. We will get to this in the third part, and I’ll cover it in my blog as well.


  19. This was really, really helpful. Chris explained a really plausible scenario for high trigylcerides during weight loss, would love to hear if there’s a similar scenario for higher LDLs (my doc has been stressing out about my LDL level — has been in the 130/140 range while I’ve been losing weight). I convinced her to do a particle test next time, and now I hear that’s not likely to be helpful … oh well ;). Good news is that at least she doesn’t want to put me on statins … she’d like to see me ingesting large amounts of oat bran instead.